Gastrointestinal Risk Research Articles

GRECO-2: A randomized, phase 2 study of stereotactic body radiation therapy (SBRT) in combination with rucosopasem (GC4711) in the treatment of locally advanced or borderline resectable nonmetastatic pancreatic cancer.

TPS4184 Background: While treatment of pancreatic cancer has advanced, survival rates remain low. Stereotactic body radiotherapy (SBRT; high dose per fraction radiation) may exhibit improved clinical outcomes in locally advanced pancreatic cancer but carries potential gastrointestinal toxicity risks (Zhong 2017). Rucosopasem (GC4711) is one of a class of investigational selective dismutase mimetics that rapidly and specifically converts superoxide to hydrogen peroxide (Riley 2006). Studies have shown that normal cells tolerate hydrogen peroxide fluxes better than cancer cells (Doskey 2016). As radiation response modifiers, dismutase mimetics have the potential to increase tumor control of SBRT without compromising radiation safety (El-Mahdy 2020, Sishc 2021). In a pilot phase 1/2 trial in patients with pancreatic cancer, avasopasem, a dismutase mimetic related to rucosopasem, nearly doubled median overall survival in patients receiving SBRT vs placebo plus SBRT. Improvements versus placebo were also observed in local tumor control, time to metastases, and progression-free survival. Altogether, these data support the hypothesis that rucosopasem may improve survival and the benefit-risk ratio of SBRT by improving efficacy without increasing gastrointestinal toxicity. Materials/Methods: GRECO-2 is a phase 2, multicenter, randomized, double-blind, placebo-controlled study (NCT04698915) to determine the effect of adding rucosopasem to SBRT on overall survival in patients with borderline resectable or locally advanced, unresectable nonmetastatic pancreatic cancer following initial chemotherapy with a FOLFIRINOX-based regimen or a gemcitabine doublet. Approximately 160 patients will be randomized (approximately 35 sites) to receive rucosopasem 100 mg or placebo via IV infusion over 15 minutes, prior to each SBRT fraction (5 x 10 Gy). Patients judged to be resectable will undergo surgical exploration within 8 weeks after SBRT. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, locoregional control, time to metastasis, surgical resection rate, RO resection rate, best overall response, in-field local response, and safety (acute and late toxicities). Exploratory endpoints include PRO-CTCAE and CA19-9 normalization. This trial is now enrolling. Clinical trial information: NCT04698915.

How Improved Is Improved Enough? Gastrointestinal Illness Risk after Sewer Infrastructure Upgrades.

How Improved Is Improved Enough? Gastrointestinal Illness Risk after Sewer Infrastructure Upgrades.

Non-steroidal anti-inflammatory drugs (NSAIDs), pain and aging: Adjusting prescription to patient features.

A narrative review of papers published from January 2011 to December 2021, after a literature search in selected databases using the terms "pharmacokinetics", "ibuprofen", "diclofenac", "acemetacin", "naproxen", "etodolac" and "etoricoxib" was performed. From 828 articles identified, only eight met the inclusion criteria. Selective COX-2 inhibitors are associated with higher cardiovascular risk, while non-selective COX inhibitors are associated with higher gastrointestinal risk. NSAIDs with lower renal excretion with phase 2 metabolism are less likely to induce adverse effects and drug-drug interactions. Patients with frequent NSAID use needs, such as elderly patients and patients with cardiovascular disease or impaired renal function, will benefit from lower renal excretion (e.g. acemethacin, diclofenac, and etodolac) (level of evidence 3). Polymedicated patients, elderly patients, and patients with chronic alcohol abuse will be at a lower risk for adverse effects with NSAIDs that undergo phase 2 liver biotransformation, namely, acemethacin and diclofenac (level of evidence 3). Young patients, patients dealing with acute pain, or with active and/or chronic symptomatic gastritis, selective COX-2 inhibitors (celecoxib or etoricoxib) may be a better option (level of evidence 2). Knowing the individual characteristics of the patients, combined with knowledge on basic pharmacology, offers greater safety and better adherence to therapy. PERSPECTIVE: Although there are several NSAIDs options to treat pain, physicians usually take special care to its prescription regarding cardiovascular and gastrointestinal side effects, despite the age of the patient. In this paper, based on the best evidence, the authors present a review of the safest NSAIDs to use in the elderly.

Factors associated with physician-reported treatment status of patients with osteoarthritis pain

BackgroundOsteoarthritis (OA) is typically associated with pain, but many patients are not treated.MethodsThis point in time study explored factors associated with treatment status, using logistic regression of data from the Adelphi OA Disease Specific Programme conducted in the United States. Patients’ treatment status was based on physician-reported, current: 1) prescription medication for OA vs. none; and 2) physician treatment (prescription medication and/or recommendation for specified nonpharmacologic treatment for OA [physical or occupational therapy, acupuncture, transcutaneous electrical nerve stimulation, or cognitive behavior therapy/psychotherapy]) vs. self-management (no prescription medication or specified nonpharmacologic treatment).ResultsThe 841 patients (including 57.0% knee OA, 31.9% hip OA) reported mild (45.4%) or moderate or severe (54.6%) average pain intensity over the last week. The majority were prescribed medication and/or recommended specified nonpharmacologic treatment; 218 were not prescription-medicated and 122 were self-managed. Bivariate analyses showed less severe patient-reported pain intensity and physician-rated OA severity, fewer joints affected by OA, lower proportion of joints affected by knee OA, better health status, lower body mass index, and lower ratings for cardiovascular and gastrointestinal risks, for those not prescribed medication (vs. prescription-medicated). Multivariate analyses confirmed factors significantly (p < 0.05) associated with prescription medication included (odds ratio): physician-rated current moderate OA severity (vs. mild, 2.03), patient-reported moderate OA severity 6 months ago (vs. mild, 1.71), knee OA (vs. not, 1.81), physician-recommended (0.28) and patient-reported (0.43) over-the-counter medication use (vs. not), prior surgery for OA (vs. not, 0.37); uncertain income was also significant. Factors significantly (p < 0.05) associated with physician treatment included (odds ratio): physician-recommended nonpharmacologic therapy requiring no/minimal medical supervision (vs. not, 2.21), physician-rated current moderate OA severity (vs. mild, 2.04), patient-reported over-the-counter medication use (vs. not, 0.26); uncertain time since diagnosis was also significant. Patient-reported pain intensity and most demographic factors were not significant in either model.ConclusionsApproximately 1 in 4 patients were not prescribed medication and 1 in 7 were self-managed, although many were using over-the-counter medications or nonpharmacologic therapies requiring no/minimal medical supervision. Multiple factors were significantly associated with treatment status, including OA severity and over-the-counter medication, but not pain intensity or most demographics.

Heterogeneity among countries in primary cardiovascular prevention guidelines: missed opportunities for adherence and improved outcomes

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Bayer AG Background · Specialty-driven guidelines identify risk factors for cardiovascular (CV) events that may potentially be modified by lifestyle or pharmacotherapy. Purpose · Worldwide, the control of modifiable risk factors in people at high cardiovascular disease (CVD) risk remains poor. Our hypothesis is that differences in multiple, specialty-driven guidelines do not help, and may hinder, the accurate assessment of CV risk factors and their appropriate management in the individual patient that has multiple risk factors or comorbidities. Methods · We conducted a review of the most recent guidelines for CVD prevention, diabetes, hypertension, dyslipidaemia and chronic kidney disease used in Europe, Italy, the USA, China and South Korea to establish the commonalities and differences between risk factor targets, risk modifiers and treatment approaches. Results · The use of low dose aspirin in patients at high risk of CVD varies between regions, and between those with and without type 2 diabetes (T2D). In addition, the use of concomitant proton pump inhibitor (PPI) treatment, that may reduce the gastrointestinal bleeding risk and therefore allow more people to be included for low dose aspirin treatment consideration, is variable (see table). · There are also differences in the definitions of risk stratification, targets for major risk factors and the use of coronary artery calcium score (CAC) to identify high-risk, asymptomatic patients. · The LDL-C targets for patients with T2D at high CV risk vary from &amp;lt;1.8 mmol/L (&amp;lt;70 mg/dL)1,2,10 to &amp;lt;2.6 mmol/L (&amp;lt;100mg/dL);9 and those for patients with T2D at very high CV risk vary from &amp;lt;1.4 mmol/L (&amp;lt;55 mg/dL)1,2 to &amp;lt;1.8 mmol/L (&amp;lt;70 mg/dL).9 · Although CAC score is identified as a risk modifier in most guidelines, its use to guide treatment decisions in patients with ≥7.5% to &amp;lt;20% 10-year ASCVD risk is recommended in only two guidelines.4,6 Conclusion(s) · We suggest that physicians cannot synthesise specialty-based recommendations for a single patient with multiple comorbidities within a limited consultation time, and that this may be a major factor in the lack of progress in managing CV risk factors. · A more unified, consistent and global approach to primary prevention of CV disease across specialties may lead to greater guideline adherence, greater patient understanding and acceptance of therapy, and improved outcomes.

Drug Safety in Episodic Migraine Management in Adults Part 1: Acute Treatments.

The aim of this review is to aid in choosing safe options when assessing potential risks of acute migraine treatments based on known mechanisms of action and anticipated safety concerns. Part 1 highlights safety issues associated with commonly used medications to treat acute migraine attacks. Strategies to mitigate cardiovascular and gastrointestinal risks of nonsteroidal anti-inflammatory drugs, evaluation of cardiovascular risks of triptan and ergot alkaloids, and precautions with use of antiemetics and the novel drugs gepants and ditans are discussed to help practitioners in clinical decision-making. When available, we included recommendations from professional societies and data from pharmacovigilance systems. While guidelines on efficacy are available, one must also consider the possible risks and adverse effects of a drug when creating treatment plans.

Gastrointestinal bleeding risk of non-vitamin K antagonist oral anticoagulants versus warfarin in general and after polypectomy: a population-based study with propensity score matching analysis.

Gastrointestinal bleeding (GIB) risk for non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin is largely unknown. We aimed to determine the risk of overall and post-polypectomy GIB for NOACs and warfarin. Using the Korean National Health Insurance database, we created a cohort of patients who were newly prescribed NOACs or warfarin between July 2015 and December 2017 using propensity score matching (PSM). Kaplan-Meier analysis with log-rank test was performed to compare the risk of overall and post-polypectomy GIB between NOACs (apixaban, dabigatran, and rivaroxaban) and warfarin. Post-polypectomy GIB was defined as bleeding within 1 month after gastrointestinal endoscopic polypectomy. Out of 234,206 patients taking anticoagulants (187,687 NOACs and 46,519 warfarin), we selected 39,764 pairs of NOACs and warfarin users after PSM. NOACs patients showed significantly lower risk of overall GIB than warfarin patients (log-rank P<0.001, hazard ratio, 0.86; 95% confidence interval, 0.78-0.94; P=0.001). Among NOACs, apixaban showed the lowest risk of GIB. In the subgroup of 7,525 patients who underwent gastrointestinal polypectomy (lower gastrointestinal polypectomy 93.1%), 1,546 pairs were chosen for each group after PSM. The NOACs group showed a high risk of post-polypectomy GIB compared with the warfarin group (log-rank P=0.001, hazard ratio, 1.97; 95% confidence interval, 1.16-3.33; P=0.012). This nationwide, population-based study demonstrates that risk of overall GIB is lower for NOACs than for warfarin, while risk of post-polypectomy GIB is higher for NOACs than for warfarin.

Meloxicam versus Celecoxib for Postoperative Analgesia after Total Knee Arthroplasty: Safety, Efficacy and Cost.

Introduction:Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used as part of multimodal analgesia in total knee arthroplasty (TKA). Selective cyclooxygenase (COX)-2 inhibitors (e.g., celecoxib) are believed to have fewer gastrointestinal (GI) adverse effects than nonselective NSAIDS. Meloxicam is less selective for COX-2 than celecoxib is and partially inhibits COX-1 at higher doses. Nonetheless, some surgeons prefer using nonselective NSAIDs because of their lower expense.Methods:Four thousand nine hundred ninety-four patients who underwent TKA between January 2015 and February 2020 and took either celecoxib (n = 3,174), meloxicam 15 mg/d (n = 1,819), or meloxicam 7.5 mg/d (n = 451) were studied. Mutlimodal postoperative analgesia protocols were otherwise similar. GI bleeding and wound complication incidence were determined, as well as average 30-day prescription costs.Results:GI bleeding incidence was similar in the three cohorts (P = 0.4). The incidence of wound complications did not significantly differ between the groups: 0.06%, 0.07%, and 0.22% in the celecoxib, meloxicam 15 mg/d, and meloxicam 7.5 mg/d groups, respectively (P = 0.06). Subsituting meloxicam for celecoxib results in an average savings of $183 per prescription.Discussion:Meloxicam used at higher doses (15 mg/d) does not markedly increase the risk of GI or wound complications associated with COX-1 inhibition and is less costly for multimodal analgesia after TKA.

The Development of a Clinical Decision-Support Web-Based Tool for Predicting the Risk of Gastrointestinal Cancer in Iron Deficiency Anaemia—The IDIOM App

To facilitate the clinical use of an algorithm for predicting the risk of gastrointestinal malignancy in iron deficiency anaemia—the IDIOM score, a software application has been developed, with a view to providing free and simple access to healthcare professionals in the UK. A detailed requirements analysis for intended users of the application revealed the need for an automated decision-support tool in which anonymised, individual patient data is entered and gastrointestinal cancer risk is calculated and displayed immediately, which lends itself to use in busy clinical settings. Human-centred design was employed to develop the solution, focusing on the users and their needs, whilst ensuring that they are provided with sufficient details to appropriately interpret the risk score. The IDIOM App has been developed using R Shiny as a web-based application enabling access from different platforms with updates that can be carried out centrally through the host server. The application has been evaluated through literature search, internal/external validation, code testing, risk analysis, and usability assessments. Legal notices, contact system with research and maintenance teams, and all the supportive information for the application such as description of the population and intended users have been embedded within the application interface. With the purpose of providing a guide of developing standalone software medical devices in academic setting, this paper aims to present the theoretical and practical aspects of developing, writing technical documentation, and certifying standalone software medical devices using the case of the IDIOM App as an example.

Patient preferences for the treatment of systemic sclerosis-associated interstitial lung disease: a discrete choice experiment.

ObjectivesTreatments for SSc-associated interstitial lung disease (SSc-ILD) differ in attributes, i.e. mode of administration, adverse events (AEs) and efficacy. As physicians and patients may perceive treatments differently, shared decision-making can be essential for optimal treatment provision. We therefore aimed to quantify patient preferences for different treatment attributes.MethodsSeven SSc-ILD attributes were identified from mixed-methods research and clinician input: mode of administration, shortness of breath, skin tightness, cough, tiredness, risk of gastrointestinal AEs (GI-AEs) and risk of serious and non-serious infections. Patients with SSc-ILD completed an online discrete choice experiment (DCE) in which they were asked to repeatedly choose between two alternatives characterized by varying severity levels of the included attributes. The data were analysed using a multinomial logit model; relative attribute importance and maximum acceptable risk measures were calculated.ResultsOverall, 231 patients with SSc-ILD completed the DCE. Patients preferred twice-daily oral treatments and 6–12 monthly infusions. Patients’ choices were mostly influenced by the risk of GI-AEs or infections. Improvement was more important in respiratory symptoms than in skin tightness. Concerning trade-offs, patients accepted different levels of increase in GI-AE risk: +21% if it reduced the infusions’ frequency; +15% if changing to an oral treatment; up to +37% if it improved breathlessness; and up to +36% if it reduced the risk of infections.ConclusionsThis is the first study to quantitatively elicit patients’ preferences for treatment attributes in SSc-ILD. Patients showed willingness to make trade-offs, providing a firm basis for shared decision-making in clinical practice.

Rebamipide as a Potential Alternative Gastroprotective Agent to Proton Pump Inhibitor in Elderly Chronic Nonsteroidal Anti-Inflammatory Drug Users without Risk Factors.

PurposeThe use of proton pump inhibitors (PPI) is recommended to prevent nonsteroidal anti-inflammatory drug (NSAID)-induced gastrointestinal (GI) complications. The incidence of several adverse effects during the long-term use of PPI prompts the search for other alternatives. Limited studies have evaluated the efficacy of rebamipide, a widely used mucoprotective drug, as a gastroprotective agent (GPA) compared to PPI, focusing on the elderly chronic NSAID users, nor with GI risk stratification. We aimed to determine the population who would get benefit from the use of rebamipide as an alternative to PPI to prevent traditional nonsteroidal anti-inflammatory drug (tNSAID)-associated GI complications.Patients and MethodsWe identified 41,889 and 35,708 elderly chronic tNSAID users with PPI and rebamipide co-therapy, respectively, from the national claims database. Outcome was defined as hospitalization or emergency department visits due to serious GI complications. Propensity score-matched cohorts were constructed and compared within risk strata.ResultsIn high and moderate risk groups with two risk factors, rebamipide showed a higher risk of serious GI complication compared to PPI (aHR 2.63, 95% CI 1.24–5.59 and aHR 2.42, 95% CI 1.21–4.83, respectively). However, in elderly patients without risk factors, there was no significant difference in the risk of serious GI complications between PPI and rebamipide (aHR 0.69, 95% CI 0.27–1.76).ConclusionThis study suggested that rebamipide can be considered as an alternative to PPI in elderly chronic tNSAID users without risk factors. However, elderly patients with other risk factors should use PPI rather than rebamipide. Therefore, the presence of GI risk factors needs to be evaluated in elderly chronic tNSAID users to prescribe the most suitable GPA in clinical practice.

Association and mechanism of garlic consumption with gastrointestinal cancer risk: A systematic review and meta-analysis.

Gastrointestinal cancer is one of the most commonly diagnosed cancer type worldwide, with millions of cases per year. The aim of this review was to investigate the relationship between garlic intake and the risk reduction of gastrointestinal cancer. We performed saturated data mining on various public domain databases, including PubMed (https://pubmed.ncbi.nlm.nih.gov/), Embase (https://www.embase.com/landing?status=grey), and Cochrane Library (https://www.cochranelibrary.com/), with key terms including: ‘garlic’, ‘allium’, ‘stomach’, ‘gastric’, ‘colon’, ‘neoplasms’, ‘cancer’ and ‘tumor’. Furthermore, we identified additional references through expert manual curation. Finally, a meta-analysis was conducted to determine whether garlic intake reduces the risk of gastric and/or colorectal cancer. The association between garlic intake and reduction in the risk of gastric cancer [odds ratio (OR)=0.65, 95% confidence interval (CI)=0.49-0.87, P<0.001] were clear. Nine studies on garlic intake and colorectal cancer showed that garlic reduced cancer risk with a statistical significance (OR=0.75, 95% CI=0.65-0.87, P<0.001). We summarized that four main organic sulfides in garlic, diallyl disulfide (DADS), diallyl trisulfide (DATS), S-allylmercaptocysteine (SAMC) and allicin, may contribute to the regulation of tumor cell apoptosis, migration and the cell cycle. We identified the association between garlic intake and reduced risk of gastric and colorectal cancers and hypothesized that the active ingredients in garlic may act on multiple pathways to reduce the risk of gastrointestinal tumors according to published papers. Importantly, the potential tumor-preventing effect of these garlic ingredients warrants further investigation in regards to the specific mechanism of the underlying antitumor activities.

Upper Gastrointestinal Cancer Surveillance in Lynch Syndrome.

Simple SummaryLynch syndrome is the most common cause of hereditary colorectal cancer, but is also associated with increased extracolonic cancer risk, including upper gastrointestinal cancers. While there is agreement regarding the benefit of frequent colonoscopic surveillance in Lynch syndrome, there remains a lack of consensus on the use of upper gastrointestinal cancer surveillance. Here, we review the upper gastrointestinal cancer risks in Lynch syndrome, the varying guideline recommendations in this area, and the published outcomes of upper gastrointestinal cancer surveillance in this high-risk population. Finally, we highlight ongoing controversies in upper gastrointestinal cancer surveillance and opine on how upper gastrointestinal cancer surveillance can be incorporated into a Lynch syndrome risk management program. Upper gastrointestinal cancer surveillance is an increasingly studied area of risk management in Lynch syndrome, and continued research will be vital in determining how to best incorporate this surveillance in these high-risk patients.Lynch syndrome is a common hereditary cancer predisposition syndrome associated with increased digestive cancer risk including colorectal, gastric, and duodenal cancers. While colorectal cancer surveillance is widely accepted to be an important part of a comprehensive Lynch syndrome risk management plan, the use of upper gastrointestinal cancer surveillance in Lynch syndrome remains more controversial. Currently, upper gastrointestinal cancer surveillance guidelines for Lynch syndrome vary widely, and there is no consensus on who should undergo upper gastrointestinal cancer surveillance, how surveillance should be performed, the age at which to initiate surveillance, or how often individuals with Lynch syndrome should undergo upper gastrointestinal cancer surveillance. Fortunately, research groups around the world have been focusing on upper gastrointestinal cancer surveillance in Lynch syndrome, and recent evidence in this field has demonstrated that upper gastrointestinal cancer surveillance can be performed with identification of precancerous lesions as well as early-stage upper gastrointestinal cancers. In this manuscript, we review the upper gastrointestinal cancer risks in Lynch syndrome, differing guideline recommendations for surveillance, outcomes of upper gastrointestinal cancer surveillance, and controversies in the field, and we provide a framework based on our collective experience with which to incorporate upper gastrointestinal cancer surveillance into a risk management program for individuals with Lynch syndrome.

Lipid-lowering drug adherence and combination therapy effects on gastrointestinal cancer in patients with dyslipidemia without diabetes: a retrospective cohort study in South Korea

BackgroundIn aging populations, the number of people with high cholesterol levels is increasing. Appropriate management of high cholesterol levels with drugs such as statins may prevent secondary diseases. Despite many studies on the effects of statins on various types of cancer, the effectiveness of lipid-lowering therapy in preventing cancer remains controversial. This study aimed to evaluate its long-term effect on developing gastrointestinal (GI) cancer in patients with dyslipidemia.MethodsThis study used the National Health Insurance Sampling (NHIS) cohort data (2002–2015), which included patients with dyslipidemia without diabetes, and measured patients’ adherence to lipid-lowering therapy using the medication possession ratio. We used the Cox proportional hazard ratio (HR) to identify the association between the continuity of lipid-lowering therapy and the risk of GI cancer. We also evaluated the association between a combination of lipid-lowering drugs and a reduced risk of GI cancer.ResultsA total of 49,351 patients were diagnosed with dyslipidemia, of which 579 were diagnosed with GI cancer. Patients with higher adherence to lipid-lowering therapy had a significantly reduced risk of GI cancer compared to patients without drugs, and high adherence was associated with a reduced incidence of all types of GI cancer. Specifically, the combination of statins and ezetimibe or fibrates appears to reduce GI cancer risk effectively. Overall, the continuity of lipid-lowering therapy had a protective effect on GI cancer in middle-aged and elderly patients with dyslipidemia compared to non-users.ConclusionsOur findings suggest that the continuity of lipid-lowering therapy is vital in patients with dyslipidemia. In addition, for individuals vulnerable to GI cancer, combination therapy may be associated with more effective protection against GI cancer. Healthcare providers need patient education and monitoring to improve drug adherence in patients with dyslipidemia.

Incidence of gastrointestinal bleeding after transoesophageal echocardiography in patients with gastro-oesophageal varices: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Transoesophageal echocardiography (TEE) is useful for cardiac assessment and intraoperative monitoring. However, the safety of TEE in cirrhotic patients with gastro-oesophageal varices has remained uncertain. Purpose This meta-analysis aims to determine the incidence of gastrointestinal bleeding after TEE in patients with varices. The secondary objectives are to compare the bleeding risks between patients with and without varices; and to determine the incidences of TEE-related oesophageal perforation and mortality. Methods Systematic literature search was conducted on MEDLINE, EMBASE and Cochrane Database using the terms "Transoesophageal echocardiography", "Varices", "Bleeding", and related terms. Articles describing the incidence of post-TEE bleeding in patients with varices were included. Non-English articles were excluded. Risk of bias was assessed through a validated scale for bias assessment in prevalence studies. The level of evidence was assessed using the Grades of Recommendation, Assessment, Development, and Evaluation approach. Pooled weighted incidence of gastrointestinal bleeding and risk difference in bleeding were calculated with a random effects model. Results 569 articles were identified initially, and 10 articles (comprising of 908 patients) were included. The incidence of post-TEE bleeding in patients with varices was 0.84% (95% CI 0.34%-1.56%). When stratified by TEE indication, the pooled incidence of bleeding was 0.68% (95% CI 0.11%-1.63%) in intraoperative TEE; and 1.03% (95% CI 0.23%-2.29%) in diagnostic TEE. No cases of oesophageal perforation or mortality were reported. 6 studies included a comparator group of patients without varices, and the bleeding risk was comparable between patients with and without varices (risk difference 0.26%; 95% CI -0.80%-1.32%; I2 = 0%, p = 0.88). Eight studies had moderate or high risk of bias, and overall level of evidence was low. Conclusion TEE appears to be associated with low gastrointestinal bleeding incidence in patients with gastro-oesophageal varices. Nonetheless, results should be treated with caution due to bias and low level of evidence. Large-scale high-quality studies will be required to confirm the safety of TEE in patients with gastro-oesophageal varices. Abstract Figure. Study selection process Abstract Figure. Forest plot of pooled bleeding incidence

Development of a multicomponent implementation strategy to reduce upper gastrointestinal bleeding risk in patients using warfarin and antiplatelet therapy, and protocol for a pragmatic multilevel randomized factorial pilot implementation trial

BackgroundThe concomitant use of anticoagulant and antiplatelet medications increases the risk of upper gastrointestinal (GI) bleeding. Two underused evidence-based practices (EBPs) can reduce the risk: de-prescribe unnecessary antiplatelet therapy or initiate a proton pump inhibitor. We describe the development of a multicomponent intervention to increase use of these EBPs in patients treated with warfarin and followed by an anticoagulation monitoring service (AMS), and the design of a pilot pragmatic implementation trial.MethodsA participatory planning group iteratively used Implementation Mapping and the Multiphase Optimization Strategy to develop implementation strategies and plan the trial. Informed by qualitative interviews with patients and clinicians, we drew on several implementation science theories, as well as self-determination theory, to design interventions. For patients, we developed an activation guide to help patients discuss the EBPs with their clinicians. For clinicians, we developed two electronic health record (EHR)-based interventions: (1) clinician notification (CN) consists of a templated message that identifies a patient as high risk, summarizes the EBPs, and links to a guidance statement on appropriate use of antiplatelet therapy. (2) Clinician notification with nurse facilitation (CN+NF) consists of a similar notification message but includes additional measures by nursing staff to support appropriate and timely decision-making: the nurse performs a chart review to identify any history of vascular disease, embeds indication-specific guidance on antiplatelet therapy in the message, and offers to assist with medication order entry and patient education. We will conduct a pilot factorial cluster- and individual-level randomized controlled trial with a primary objective of evaluating feasibility. Twelve clinicians will be randomized to receive either CN or CN+NF for all their patients managed by the AMS while 50 patients will be individually randomized to receive either the activation guide or usual care. We will explore implementation outcomes using patient and clinician interviews along with EHR review.DiscussionThis pilot study will prepare us to conduct a larger optimization study to identify the most potent and resource conscious multicomponent implementation strategy to help AMSs increase the use of best practices for upper GI bleeding risk reduction.Trial registrationClinicalTrials.gov NCT05085405. Registered on October 19, 2021—retrospectively registered.

High-density lipoprotein, low-density lipoprotein and triglyceride levels and upper gastrointestinal cancers risk: a trans-ancestry Mendelian randomization study.

This study was conducted to explore the causal associations of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglyceride (TG) with the risk of upper gastrointestinal cancers (esophageal cancer [EC] and gastric cancer [GC]). A total of 5623 Chinese and 4133 Europeans afforded the individual-level genotyping data, and 203,608 Japanese from Biobank Japan project and 393,926 Europeans from UK Biobank supported summary statistics of cancer genetic associations. Mendelian randomization (MR) analyses, including weighted genetic risk scores (wGRSs), inverse-variance weighted (IVW), weighted median and Egger-regression, were utilized to evaluate the causal effects of three blood lipids on upper gastrointestinal cancers risk. There was no significantly causal relationships between three blood lipids and EC or GC risk among Chinese or Europeans but a potential causal association between TG and GC risk among Japanese (IVW: odds ratio [OR] = 1.11, P = 0.034; Phet = 0.679). In stratified subgroups, higher genetically predicted TG levels were causally associated with an increased risk of GC among Chinese males (wGRS: OR = 1.61, P = 0.021; IVW: OR = 1.57, P = 0.009; Phet = 0.653) and Japanese females (IVW: OR = 1.33, P = 0.024; Phet = 0.378). This trans-ancestry MR study suggested null significant causality between serum HDL, LDL or TG and the risk of upper gastrointestinal cancers among Chinese and Europeans, but provided evidence for a causal role of TG involved in GC etiology in Japanese (especially females), which would support a prevention guide for high-risk groups of GC. Further research with more comprehensive information is needed to explore the underlying mechanism.

Design, synthesis, and pharmacological evaluation of novel and selective COX-2 inhibitors based on celecoxib scaffold supported with in vivo anti-inflammatory activity, ulcerogenic liability, ADME profiling and docking study

Four new series of 1,2,4 triazole derivatives 4a,b 5a-d, 6a-f, and 7a,b possessing methylsulphonylphenyl moiety as COX-2 pharmacophore were designed and synthesized. The target compounds were prepared and evaluated in-vitro against COX-1 and COX-2 enzymes. Compounds 4a, 5b, 6a, and 7a showed the highest selectivity towards the COX-2 enzyme (S.I. = 8.64–14.58) in comparison to celecoxib (S.I. = . 6.44). Interestingly, compounds 4a, 6a, and 7a showed good anti-inflammatory activity with edema inhibition (54.17, 53.03, and 50.29 %, in order) relative to the reference drug celecoxib (49.60%) after 3 h. Additionally, these potent derivatives 4a, 5b, 6a and 7a were significantly less ulcerogenic (U.I. = 2.27–2.97) than both reference drugs celecoxib (U.I. = 2.99) and indomethacin (U.I. = 20.25). Besides, a histopathological study of the stomach was also included. Moreover, docking simulation for the most selective compounds 4a, 5b, 6a, and 7a inside COX-2 active site was performed to explain their binding mode. Finally, an ADME study was applied and proved the promising activity of the new compounds as a new oral anti-inflammatory agent. In conclusion, the above findings reveal that newly developed compounds 4a, 6a, and 7a represent a potential selective COX-2 NSAID candidate with minimum gastrointestinal risks.

Análisis y evaluación del riesgo cardiovascular y gastrointestinal de los antiinflamatorios no esteroideos inhibidores selectivos y no selectivos de ciclooxigenasa

Introduction: the aim of this study is to review the current evidence on the clinical use of NSAIDs, coxibs and nonselective, and to evaluate its cardiovascular (CVR) and gastrointestinal risk (GIR) by means of a meta-analytic procedure. Materials and methods: cohort and case-control studies showing CVR and GIR associated with NSAIDs versus no treatment were selected. We estimated the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and individually. Results: both coxibs (RR, 1.22 [95%CI, 1.17-1.28]) and nonselective NSAIDs (RR 1.18 [95%CI, 1.12-1.24]) were associated with an increased CVR. The coxibs CVR remained even for low-dose and low-baseline CVR subgroups. Analysis by drug disclosed that rofecoxib (RR 1.39 [95%CI, 1.31- 1.47]), along with diclofenac (RR, 1.34 [95%CI, 1.26-1.42]) and etoricoxib (RR 1.27 [95%CI, 1.12-1.43]) were the NSAIDs associated with the highest CVR. Gastrointestinal risk meta-analysis showed that coxibs were associated with a GIR increment [RR1.64 (95% CI 1.44-1.86)]. Analysis by drug disclosed that etoricoxib [RR 4.48 (95% CI 2.98-6.75)]presented the highest GIR followed by rofecoxib [RR 2.02 (95% CI 1.56-2.61)] and celecoxib [RR1.62 (95% CI 1.46-1.78)]. GIR was also high for &lt;65 year-old and low-dose coxibs subgroups. Conclusion: according to our study the use of NSAIDs (coxibs and nonselective) are associated with a similar CVR increment, even for low-dose and low-baseline CVR subgroups. On the other hand, the use of coxibs is associated with a GIR increased, which would be high even for low-dose coxibs and &lt;65-year-old subgroups. The risk would be higher for etoricoxib than for celecoxib and rofecoxib. Keywords: adverse drug reactions; nonsteroidal anti-inflammatory drugs; cardiovascular risk; meta-analysis; observational studies; cyclo-oxygenase 2 inhibitor; gastrointestinal events

The Prevalence of Blastocystis sp. and Its Relationship with Gastrointestinal Disorders and Risk factors.

Background:Blastocystis sp., located in the large intestine, is one of the most common zoonotic parasites. Risk factors affect its prevalence and pathogenicity, and it causes gastrointestinal disorders. Thus, this study aimed to investigate the Blastocystis sp. prevalence and its relationship with gastrointestinal disorders, in patients referred to laboratories, and provide some prevention strategies.Methods:In this descriptive-analytical study, 1,000 stool specimens were collected from patients referred to Ilam, Iran laboratories from 2018–2019. Wet mount method was conducted on samples, and suspected specimens were confirmed using trichrome staining. The demographic and clinical information was recorded in a questionnaire. Finally, the results were analyzed using the SPSS.Results:Blastocystis infection was detected in 81 out of 1,000 patients (8.1%) including 61 (75.3%) males and 20 (24.7%) females. and illiterate people were more at risk. The prevalence in rural was more than urban areas, and it was more in the age group of 31–50 year.Conclusion:There was a significant relationship between Blastocystis sp. and risk factors (age, sex, level of education, and residence) and clinical symptoms (stomach ache and nausea) (P<0.05), but interestingly there was no significant relationship between bloating and diarrhea.